Red blood cells are made up of water and proteins such as hemoglobin, and cell membranes thereof consist mainly of water, lipids, proteins, and carbohydrates. Mature red blood cells are the most common type of blood cells involved in blood circulation. As for the morphology of a red blood cell, a red blood cell (often referred to as a discocyte) has a flexible membrane of a double-sided concave shape that is optimal for maximum deformation, maximum surface exposure at a given volume, and rapid morphological changes during passage through small capillaries in microcirculation.
In particular, since the internal structure of a red blood cell is not complicated, the double-sided concave shape of a red blood cell is regarded as a result of minimizing the free energy of the cell membrane under the above-mentioned area and volume limitations. Red blood cells must adapt to capillaries having a relatively wide range of sizes in blood vessels, but red blood cells must be able to deform while maintaining cell integrity and functions thereof. Such deformation is possible because red blood cells do not have a three-dimensional cytoskeleton. On the other hand, the morphology and mechanical integrity of red blood cells can be maintained, at the time of the deformation, by two-dimensional triangular lattices formed by flexible spectrin tetramers linked by actin oligomers. Since the lateral length (70 to 80 nm) of actin is shorter than the contour length (about 200 nm) of a spectrin tetramer, spectrin is considered to act as a major contributor to the bending modulus or curvature of red blood cells.
Conventionally, biochemical methods were applied to measure parameters required for measuring the condition of red blood cells, and thus it was difficult to measure red blood cell membrane fluctuations.